Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats

1989 ◽  
Vol 120 (2) ◽  
pp. 331-336 ◽  
Author(s):  
E. M. Whitaker ◽  
A. C. Robinson
Keyword(s):  
Preoptic Area ◽  
Plasma Concentrations ◽  
Underlying Mechanism ◽  
Reproductive Hormones ◽  
Oestrous Cycle ◽  
Zucker Rats ◽  
Medial Basal Hypothalamus ◽  
Progestin Receptors ◽  
Obese Rats ◽  
The Difference

ABSTRACT Plasma concentrations of LH, FSH, prolactin and progesterone were measured during the oestrous cycle in obese (fa/fa) and non obese (Fa/?) Zucker rats. In obese rats the mid-afternoon surge of LH during prooestrus was reduced compared with that in non-obese rats (P<0.05), and the maximum concentrations of FSH and prolactin declined more slowly during oestrus. Progesterone concentrations were higher during most of the oestrous cycle in obese rats. Oestradiol and progestin receptors were measured in the hypothalamus of female Zucker rats. Lower concentrations of oestradiol receptors were found in the preoptic area of obese rats (P<0.05). Concentrations of oestradiol receptors in the medial basal hypothalamus were also lower in obese rats, though the difference was not statistically significant. Concentrations of progestin receptors were similar in both phenotypes in the preoptic area and media basal hypothalamus. It seems likely that the abnormalities in reproductive hormones and oestradiol receptors contribute to the infertility of obese female Zucker rats. The underlying mechanism has still to be determined. Journal of Endocrinology (1989) 120, 331–336

Plasma oestradiol-17β and testosterone concentrations as possible causes of the infertility of congenitally obese Zucker rats

1983 ◽  
Vol 99 (3) ◽  
pp. 485-490 ◽  
Author(s):  
E. M. Whitaker ◽  
M. A. Shaw ◽  
G. R. Hervey
Keyword(s):  
Plasma Concentrations ◽  
Gonadal Hormones ◽  
Oestrous Cycle ◽  
Zucker Rats ◽  
Obese Female ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Mean ◽  
Plasma Oestradiol ◽  
Mean Concentration

The plasma oestradiol-17β concentrations of obese and non-obese female Zucker rats have been measured in three phases of the oestrous cycle. The oestradiol concentrations of both phenotypes were similar, and changed normally with the oestrous cycle. The weights of the uteri also changed normally with the cycle. Plasma androgen concentrations in male Zucker rats have also been measured: the mean concentration was slightly but significantly lower in obese rats, and androgen-sensitive tissues were slightly reduced in weight. The oestradiol-17β concentrations in males of both phenotypes were similar. It seems unlikely that deficient plasma concentrations of gonadal hormones cause the infertility of obese rats of either sex.

Effect of changing body temperature on the ventilatory and metabolic responses of lean and obese Zucker rats

1998 ◽  
Vol 275 (2) ◽  
pp. R531-R540 ◽  
Author(s):  
Michael Maskrey ◽  
David Megirian ◽  
Gaspar A. Farkas
Keyword(s):  
Body Temperature ◽  
Breathing Pattern ◽  
Ventilation Rate ◽  
Zucker Rats ◽  
Obese Rats ◽  
Shallow Breathing ◽  
Obese Zucker Rats ◽  
Metabolic Variables ◽  
The Difference ◽  
Rapid Shallow Breathing

We measured body temperature (Tb) and ventilatory and metabolic variables in lean ( n = 8) and obese ( n = 8) Zucker rats. Measurements were made while rats breathed air, 4% CO2, and 10% O2. Under control conditions, Tb in obese rats was always less than that of their lean counterparts. Obese rats adopted a more rapid, shallow breathing pattern than lean rats in air and had a lower ventilation rate in 4% CO2. Respiration in 10% O2 was similar for the two groups. Metabolic variables did not differ between lean and obese rats whatever the gas breathed. When lean rats were cooled to match Tb in control obese rats with an implanted abdominal heat exchanger, they increased ventilation and metabolism in air; there was no effect of cooling on responses to 4% CO2; and ventilation increased while metabolism decreased in 10% O2. When obese rats were warmed to match Tb in control lean rats, trends in ventilation and metabolism resulted in a tendency toward hyperventilation in air and 4% CO2, but not in 10% O2. Taken overall, matching Tb in lean and obese rats accentuated differences in respiratory and metabolic variables between the two groups. We conclude that differences in respiration between lean and obese Zucker rats are not due to the difference in Tb.

Impaired Insulin-Induced Attenuation of Noradrenaline-Mediated Vasoconstriction in Insulin-Resistant Obese Zucker Rats

1997 ◽  
Vol 93 (3) ◽  
pp. 235-241 ◽  
Author(s):  
A. B. Walker ◽  
J. Dores ◽  
R. E. Buckingham ◽  
M. W. Savage ◽  
G. Williams
Keyword(s):  
Underlying Mechanism ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Obese Zucker Rat ◽  
Maximal Tension ◽  
Impaired Insulin ◽  
Obese Rats ◽  
Significant Impairment ◽  
Obese Zucker Rats ◽  
L 13

1. Insulin resistance is associated with hypertension but the underlying mechanism is unclear. We tested the hypothesis that insulin-induced vasodilatation is impaired in insulin-resistant obese Zucker rats. We studied mesenteric artery (≈ 220 μm diameter) function before the development of hypertension in 3-month old obese Zucker rats and age-matched lean rats. 2. In vessels from lean rats, insulin at concentrations of 50, 500 and 5000 m-units/l attenuated the constriction in response to noradrenaline (50 m-units/l: 8 ± 3%, P < 0.05; 500 m-units/l: 13 ± 3%, P < 0.02; 5000 m-units/l: 13 ± 2%, P < 0.02). 3. Vessels from obese rats failed to show any such response to insulin (2 ± 6% increase in maximal tension with 5000 m-units/l; not significant), both in the presence and absence of l-arginine (3 mmol/l). 4. Vessels from obese rats showed slight but significant impairment in the vasodilator response to acetylcholine (5 × 10−8−10−4 mol/l) (obese: 64.1 ± 3.7% relaxation; lean: 77.3 ± 3.7% relaxation; P < 0.05); however, relaxation in response to A23187 was not significantly different between the phenotypes (obese: 81.3 ± 10.6% relaxation; lean: 79.1 ± 9.7% relaxation; not significant). 5. Systolic blood pressure was not significantly different in lean (126 ± 8 mmHg) and obese (127 ± 7 mmHg) rats at the time of study (not significant). 6. We conclude that insulin-induced attenuation of noradrenaline-mediated vasoconstriction is impaired in the obese Zucker rat and that this defect precedes and therefore could contribute to the development of hypertension in this insulin-resistant model. The defect in insulin action could reside in the endothelial generation of nitric oxide, as endothelial function is also abnormal.

scholarly journals Mechanisms of dysregulation of 11 beta-hydroxysteroid dehydrogenase type 1 in obese Zucker rats

2000 ◽  
Vol 167 (3) ◽  
pp. 533-539 ◽  
Author(s):  
DE Livingstone ◽  
CJ Kenyon ◽  
BR Walker
Keyword(s):  
Weight Gain ◽  
Hydroxysteroid Dehydrogenase ◽  
Zucker Rats ◽  
Tissue Specific ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Difference ◽  
Underlying Mechanisms ◽  
Omental Fat

Obesity has been associated with alterations in glucocorticoid metabolism in both man and rodents, but the underlying mechanisms remain undefined. We have previously reported tissue-specific alterations in 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) in obese Zucker rats predicting that reactivation of corticosterone is decreased in liver but increased in omental fat. The mechanisms of dysregulation of 11 beta-HSD1 in obesity are not known, and in this study we have investigated the potential role of glucocorticoids and insulin. In one experiment lean and obese Zucker rats were adrenalectomised, and in a second experiment they were sensitised to insulin by treatment with either metformin or rosiglitazone. Adrenalectomy (ADX) of obese animals attenuated weight gain, normalised hepatic 11 beta-HSD1 kinetics by an effect on V(max) (V(max)in sham-operated animals, 6.6+/-1.1 nmol/min per mg in lean vs 3.4+/-0.6 in obese, P<0.01; in ADX animals 5.9+/-1.1 in lean vs 6.9+/-1.8 in obese, NS), and reversed the difference in omental fat 11 beta-HSD1 activity (18.9+/-4.2% in lean ADX vs 8.2+/-2.3 in obese ADX, P=0.03). Both metformin and rosiglitazone improved insulin sensitivity in obese, but not lean animals, and had no effect on 11 beta-HSD1 activity in either liver or fat. However, both treatments normalised adrenal hypertrophy in obese animals (48+/-29 mg in obese vehicle vs 37+/-1.2 in metformin and 38+/-1.8 in rosiglitazone treated, both P<0.01), and rosiglitazone tended to attenuate hypercorticosteronaemia in obese rats. Neither treatment attenuated weight gain; in fact, weight gain was enhanced by rosiglitazone in obese rats. In summary, altered 11 beta-HSD1 activity in obese Zucker rats is reversible following adrenalectomy, but the mechanism is unclear since adrenalectomy also normalises many other metabolic abnormalities. The current study suggests that hyperinsulinaemia is not responsible for tissue-specific dysregulation of 11 beta-HSD1. However, insulin sensitisation did reverse adrenal hypertrophy, suggesting that hyperinsulinaemia may be a key factor contributing to activation of the hypothalamic- pituitary-adrenal (HPA) axis in obesity independently of tissue-specific changes in 11 beta-HSD1.

scholarly journals Species Differences in Stereoselective Pharmacokinetics of HSG4112, A New Anti-Obesity Agent

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 127
Author(s):  
In Yong Bae ◽  
Min Sun Choi ◽  
Young Seok Ji ◽  
Sang-Ku Yoo ◽  
Kyungil Kim ◽  
...  
Keyword(s):  
Species Difference ◽  
Plasma Concentrations ◽  
Liver Microsomes ◽  
Underlying Mechanism ◽  
Rat Plasma ◽  
Rat Liver Microsomes ◽  
Stereoselective Metabolism ◽  
Stereoselective Pharmacokinetics ◽  
The Difference ◽  
Dog Liver

HSG4112, a racemic drug, is a new anti-obesity agent. In this study, the stereoselective pharmacokinetics of HSG4112 were investigated in rats and dogs, and the underlying mechanism was investigated. The plasma concentrations of HSG4112(S) and HSG4112(R) were quantitated in plasma from rats and beagle dogs after IV and/or oral administration of racemic HSG4112. The concentration of HSG4112(S) was significantly higher than that of HSG4112(R) in rat plasma. Contrarily, the concentration of HSG4112(R) was significantly higher than HSG4112(S) in dog plasma. A metabolic stability test with liver microsomes showed that HSG4112(S) was more stable than HSG4112(R) in rat liver microsomes, but the difference between stereoisomers did not appear in dog liver microsomes. However, the stereoselectivity was observed in dog liver and intestinal microsomes after uridine 5’-diphospho-glucuronic acid was added. Thus, stereoselective metabolism by uridine 5’-diphospho-glucuronosyltransferases is mainly responsible for the stereoselective pharmacokinetics in dogs. These results suggest that the species difference in the stereoselective plasma pharmacokinetics of HSG4112 is due to the stereoselective metabolism.

Effects of day length on sheep neuroendocrine estrogen and progestin receptors

1990 ◽  
Vol 258 (1) ◽  
pp. R135-R142
Author(s):  
E. L. Bittman ◽  
J. D. Blaustein
Keyword(s):  
Estrogen Receptor ◽  
Binding Site ◽  
Hormone Receptors ◽  
Preoptic Area ◽  
Steroid Hormone Receptors ◽  
Day Length ◽  
Medial Basal Hypothalamus ◽  
Progestin Receptors ◽  
Binding Characteristics ◽  
Nuclear Estrogen Receptor

Gonadal steroid hormone receptors were studied in anterior pituitary, preoptic area, and hypothalamus of ovariectomized ewes. We established that systemic administration of estradiol benzoate elevates levels of nuclear estrogen receptor concentrations and results in the appearance of cytosolic progestin receptor the binding characteristics of which are comparable with that reported in rats and guinea pigs [0.1 nM Kd, binding site density (Bmax) of 111, 22, and 2 fmol/mg protein in pituitary, medial basal hypothalamus, and preoptic area, respectively]. Brain tissues also contained a second, low-affinity progestin binding site. To examine possible effects of photoperiod on neuroendocrine steroid receptors, two groups of sheep were exposed to artificial photoperiods. Ewes experienced alternating periods of long (LD 16:8) or short (LD 8:16) days for 290 days to induce breeding season or anestrous states. Animals were then ovariectomized and given steroid treatments designed to mimic a luteal phase followed by either follicular phase levels of estradiol or withdrawal of all exogenous hormones before determination of neuroendocrine steroid receptor concentrations. Despite the ability of long photoperiods to arrest ovarian cyclicity, magnify negative feedback actions of estradiol upon luteinizing hormone, and reduce the ability of estrogen to trigger behavioral estrus, photoperiod did not influence nuclear estrogen receptor concentrations or the induction of cytosolic progestin receptors in the pituitary, hypothalamus, or preoptic area.

FSH AND LH LEVELS IN THE INTACT AND UNILATERALLY OVARIECTOMIZED CYCLING RAT

1972 ◽  
Vol 69 (2) ◽  
pp. 267-280 ◽  
Author(s):  
Richard D. Peppler
Keyword(s):  
Plasma Concentrations ◽  
Follicular Development ◽  
Slight Modification ◽  
Oestrous Cycle ◽  
Successive Cycle ◽  
Unilateral Ovariectomy ◽  
Subsequent Cycle ◽  
Intact Rats

ABSTRACT Intact 5-day cycling rats were killed between 8–10 a. m. on each day of the oestrous cycle; experimental rats were unilaterally ovariectomized (ULO) at 9 a. m. on day 1 (oestrus) and killed between 8 and 10 a. m. on days 2, 3, 4 or 1 of the subsequent cycle. Pituitary and plasma concentrations of FSH and LH were measured in both groups of rats. Pituitary FSH concentration was measured by the Steelman-Pohley method with slight modification; plasma FSH by the Igarashi-McCann assay and pituitary and plasma LH concentration by the OAAD method. In intact rats, pituitary FSH values remained constant for the first three days of the cycle, increased on day 4 and reverted to early cycle values by day 5. Plasma FSH increased between days 2 and 3 and days 5 and 1. Pituitary LH concentration remained the same for days 1 and 2; increased two-fold on days 3 and 4, and increased further by day 5. Plasma LH increased between days 2 and 3; other differences between successive cycle days were not apparent. Following ULO on day 1, pituitary FSH increased steadily, but not significantly, for the remaining cycle. Plasma FSH did not change from day 2 through day 1 of the subsequent cycle. Pituitary LH remained low on day 2, increased sharply by day 3 and decreased (50 %) by day 4. Plasma LH also increased between days 2 and 3. Other differences between successive days following unilateral ovariectomy on day 1 were not apparent. Correlation of gonadotrophin activity with follicular development suggests that the mechanism of compensatory ovulation in the rat may be one of an increase in time of exposure to a constant gonadotrophic level for the duration of the oestrous cycle rather than to increased levels of the gonadotrophin.

Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos cinereus)

Reproduction ◽  
2000 ◽  
pp. 49-57 ◽  
Author(s):  
SD Johnston ◽  
MR McGowan ◽  
P O'Callaghan ◽  
R Cox ◽  
V Nicolson
Keyword(s):  
Luteal Phase ◽  
Post Partum ◽  
Plasma Concentrations ◽  
External Genitalia ◽  
Oestrous Cycle ◽  
Phascolarctos Cinereus ◽  
Pregnant Females ◽  
Peripheral Plasma ◽  
The Mean ◽  
High Concentrations

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.

scholarly journals High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT2R-MasR axis in obese Zucker rats

2012 ◽  
Vol 303 (3) ◽  
pp. F412-F419 ◽  
Author(s):  
Preethi Samuel ◽  
Quaisar Ali ◽  
Rifat Sabuhi ◽  
Yonnie Wu ◽  
Tahir Hussain
Keyword(s):  
Sodium Intake ◽  
Zucker Rats ◽  
Kidney Cortex ◽  
Complex Nature ◽  
Ang Ii ◽  
Pronounced Increase ◽  
High Sodium ◽  
High Sodium Intake ◽  
Obese Rats ◽  
Obese Zucker Rats

High sodium intake is known to regulate the renal renin-angiotensin system (RAS) and is a risk factor for the pathogenesis of obesity-related hypertension. The complex nature of the RAS reveals that its various components may have opposing effects on natriuresis and blood pressure regulation. We hypothesized that high sodium intake differentially regulates and shifts a balance between opposing components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II-type 1 ANG II receptor (AT1R) vs. AT2-ACE2-angiotensinogen (Ang) (1–7)-Mas receptor (MasR), in obesity. In the present study, we evaluated protein and/or mRNA expression of angiotensinogen, renin, AT1A/BR, ACE, AT2R, ACE2, and MasR in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and obese Zucker rats. The expression data showed that the relative expression pattern of ACE and AT1BR increased, renin decreased, and ACE2, AT2R, and MasR remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese rats caused an increase in the cortical expression of ACE, a decrease in ACE2, AT2R, and MasR, and no changes in renin and AT1R. The cortical levels of ANG II increased by threefold in obese rats on HS compared with obese rats on normal salt (NS), which was not different than in lean rats. The HS intake elevated mean arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This study suggests that HS intake causes a pronounced increase in ANG II levels and a reduction in the expression of the ACE2-AT2R-MasR axis in the kidney cortex of obese rats. We conclude that such changes may lead to the potentially unopposed function of AT1R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension.

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